Personalised service? Changing the role of the government librarian

Investigates the feasibility of personalised information service in a government department. A qualitative methodology explored stakeholder opinions on the remit, marketing, resourcing and measurement of the service. A questionnaire and interviews gathered experiences of personalised provision across the government sector. Potential users were similarly surveyed to discuss how the service could meet their needs. Data were analysed using coding techniques to identify emerging theory. Lessons learned from government librarians centred on clarifying requirements, balancing workloads and selective marketing. The user survey showed low usage and awareness of existing specialist services, but high levels of need and interest in services repackaged as a tailored offering. Fieldwork confirmed findings from the literature on the scope for adding value through information management advice, information skills training and substantive research assistance and the need to understand business processes and develop effective partnerships. Concluding recommendations focus on service definition, strategic marketing, resource utilisation and performance measurement

Patterns of winter occurrence of three sympatric killer whale populations off eastern Vancouver Island, Canada, based on passive acoustic monitoring

Understanding habitat use patterns of animal populations across space and time is fundamental to identifying ecological requirements, and informing threat mitigation and conservation strategies. Persistent data gaps tend to occur with cryptic species in difficult-to-access environments, where the use of appropriate monitoring tools is indispensable for detection. Three populations of threatened and endangered killer whales occur year-round in waters off British Columbia, Canada; however, their winter habitat use patterns are not well known. Here we quantify wintertime use of the northern Strait of Georgia by these sympatric killer whale populations, revealing the importance of this previously understudied region. Using a network of passive acoustic monitoring devices deployed over three winter periods, we examine site-specific and regional patterns of occurrence of Bigg’s, and Southern and Northern Resident killer whales. All three populations frequented these waters in nearly every month from November to April, and across all study years. Bigg’s killer whales were detected most frequently, followed by Southern Residents, then Northern Residents. Population-specific differences in site use was apparent, with Southern Resident detections occurring more often than expected off the southwest side of Texada Island, while Northern Residents appeared to favor the east side of Texada Island. Remarkably, the patterns of winter use we observe in this region by Resident killer whale populations have seemingly persisted for at least 50 years. Additionally, we evaluate and discuss the effect of using multiple simultaneous recorders to characterize habitat use patterns. Lastly, we present a data-driven approach for estimating acoustic residence time, describe inter-population differences in winter residency in the northern Strait of Georgia, and discuss implications for critical habitat designation. This study fills important knowledge gaps related to killer whale winter occurrence off western Canada, highlighting the significance of the northern Strait of Georgia for these at-risk populations

A Novel Tropically Stable Oral Amphotericin B Formulation (iCo-010) Exhibits Efficacy against Visceral Leishmaniasis in a Murine Model

Visceral leishmaniasis (VL) is a systemic form of a vector-borne parasitic disease caused by obligate intra-macrophage protozoa of the genus Leishmania. VL is always fatal in humans if left untreated and treatment options are limited. Amphotericin B (AmB), a polyene antibiotic, is the most active antileishmanial agent that currently exists. Liposomal AmB (AmBisome) is used as first-line treatment in developed countries [1], [7], [8], [9], [10]; however, the requisite parenteral administration and the high cost of the liposomal formulation prevents this treatment from reaching the majority of patients in developing nations [3]. A stable, efficacious oral treatment for VL that is able to withstand the rigors of tropical climates would overcome many of the current barriers to treatment that exist in countries with large VL-infected patient populations. In this study we have developed an oral formulation of AmB that is stable in tropical conditions and exhibits significant antileshimanial activity in mice

Divergent foraging strategies between populations of sympatric matrilineal killer whales

In cooperative species, human-induced rapid environmental change may threaten cost–benefit tradeoffs of group behavioral strategies that evolved in past environments. Capacity for behavioral flexibility can increase population viability in novel environments. Whether the partitioning of individual responsibilities within social groups is fixed or flexible across populations is poorly understood, despite its relevance for predicting responses to global change at the population and species levels and designing successful conservation programs. We leveraged bio-logging data from two populations of fish-eating killer whales (Orcinus orca) to quantify patterns of fine-scale foraging movements and their relationships with demography. We reveal striking interpopulation differences in patterns of individual foraging behavior. Females from the endangered Southern Resident (SRKW) population captured less prey and spent less time pursuing prey than SRKW males or Northern Resident (NRKW) females, whereas NRKW females captured more prey than NRKW males. The presence of a calf (≤3 years) reduced the number of prey captured by adult females from both populations, but disproportionately so for SRKW. SRKW adult males with a living mother captured more prey than those whose mother had died, whereas the opposite was true for NRKW adult males. Across populations, males foraged in deeper areas than females, and SRKW captured prey deeper than NRKW. These population-level differences in patterns of individual foraging behavior challenge the existing paradigm that females are the disproportionate foragers in gregarious resident killer whales, and demonstrate considerable variation in the foraging strategies across populations of an apex marine predator experiencing different environmental stressors

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant